White and light skin is preferred by the majority of people. Numerous skin-care products for skin-whitening and anti-skin-aging have been developed for both cosmetic and medicinal applications. However, products containing synthesized chemicals always carry adverse effects. For example, hydroquinone-containing products for skin bleaching exhibit adverse effects such as exogenous ochronosis and leukoderma-en-confetti/occupational vitiligo. Since 2001, hydroquinone has been forbidden in the European Union to be used as an ingredient for cosmetics. In addition, some natural components-containing products also exhibit some disadvantages for skin care. For examples, kojic acid is not stable and causes skin irritations; and arbutin presents weak effect in skin-whitening.
Oxidative stress plays a central role in initiating and driving events that cause skin aging at cellular level. It has been widely accepted that the formation of free radicals plays a pivotal mechanism leading to skin aging. Scavenging of reactive oxygen species can protect skin cells from free radicals induced damages. Currently, topical antioxidants, such as vitamin A, have been widely used in over-the-counter skin care products. However, vitamin A-containing products have adverse effects including redness, scaling, burning, and itching.
Therefore, development of a tailored product with high potency for skin-whitening and anti-skin-aging has been focused by many researchers and cosmetic industries.
Skin color is determined by the content of melanin dispersed in epidermis. Biosynthesis of melanin (also called melanogenesis) occurs in melanocytes and catalyzes by three enzymes named tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2). Among them, TYR has been identified as the rate-limiting enzyme for melanin biosynthesis. Inhibition of cellular TYR activity can effectively decrease melanogenesis thus whitening the skin. Most current commercial cosmetic products for skin-whitening are TYR inhibitors.
Biologically, the transcription of genes encoding TYR and TRP-1 is under the control of microphthalmia transcription factor (MITF), which is regulated by the Wnt signaling pathway, the p38 signaling pathway and the mitogen-activated protein (MAP) kinase pathways as well as by cyclic adenosine 3′,5′-monophosphate/protein kinase A/cAMP response element binding protein (cAMP/PKA/CREB) pathway. Any agents that regulate these signaling pathways also have the potential to affect MITF thus melanogenesis. Therefore, combination of different compounds with multi-targets for regulating MITF is more effective on skin-whitening than single compound with single target.
Improvement of the skin conditions, i.e. anti-skin-aging, to accelerate melanin elimination from the epidermis is another strategy for skin-whitening. Scavenging of free radicals can help skin-whitening and prevent skin aging. A good skin-care product should have multiple functions such as skin-whitening and anti-skin-aging.
Citation or identification of any reference in this section or any other section of this application shall not be construed as an admission that such reference is available as prior art for the present application.